This proposal plans to use cell culture techniques to investigate genetic dwarfism syndromes as possible inborn errors of cell growth. This group of patients is comprised of many syndromes which have no endocrine or metabolic explanation for their dwarfing. The patients have been described as having cellular resistance to growth promoting factor, with no direct evidence for this assumption. We have reasoned that, if cells from these patients do respond poorly to growth stimulators and do grow slowly, cell culture techniques should be useful in documenting and investigating this behavior. To initiate this study, we must assemble and categorize these patients. We then plan to measure somatomedin levels in their blood and obtain skin biopsies for fibroblast cultures to be studied. A unique approach in this proposal is the use of fibroblast growth factor, FGF, a pure somatomedin-like peptide which can, in defined medium, sequentially stimulate transport, RNA synthesis, and DNA synthesis in human fibroblasts. This will allow us to systematically examine several processes important in cell division. If errors can be identified, we can then proceed to more detailed investigation which may yield not only information about etiology but also means for more precise diagnosis - possibly prenatally. If cells with growth defects can be identified, they may provide a valuable pool of naturally occurring, varied mutants for the further investigation of mechanisms of cell growth.